This project is concerned with basic tumor biology. Human tumor cells and their normal counterparts are being isolated, some types for the first time, by Dr. Rheinwald. He is learning how their anaplastic and neoplastic properties are exhibited in culture. Normal and defective differentiation are also being studied by Dr. Gudas, using molecular genetic techniques. The key role in growth regulation of normal and tumor cells by platelet-derived growth factor (PDGF) is being investigated at cellular, biochemical and molecular genetic levels by Dr. Stiles, including possible relations to oncogenes. The importance of genetic rearrangements in human cancer has become increasingly more evident. Dr. Sager, one of the first to recognize this fact, is doing elegant experiments with human and rodent cells to study the mechanisms that bring about these changes. Along related lines, Drs. Szostak and Maxam are probing gene structures and arrangements, using sophisticated and delicate molecular techniques. Dr. Chen is identifying cancer cells using dyes novel for this purpose, Rhodamines. He has found these dyes to be selectively toxic to some tumor cells. Lethality of DNA damaging agents toward human cells is increased greatly by preventing repair of the DNA lesions. Dr. Pardee is adding DNA repair inhibitors to chemotherapy with a view to improving the specificity and efficacy of the antineoplastic drugs.